This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Previous efforts to adapt HIV-1 for replication in rhesus macaques have not addressed the susceptibility of the virus to rhesus tetherin or polymorphic differences in rhesus TRIM5alpha. The goal of these studies is to adapt HIV-1 for replication in rhesus macaques by introducing changes into the viral genome that confer resistance to rhesus tetherin and specific alleles of TRIM5 alpha.